Human growth hormone (hGH) is multifaceted from both a functional and a chemical standpoint. The variety of different activities exhibited by hGH has been known for some time. More recently, it was recognized that monomeric hGH consists of several components (isohormones B, C, D and E). HGH-C, D and E are proteolytic cleavage products of the intact form, hGH-B. HGH-D and E exhibit significantly enhanced overall growth promoting activity compared to standard hGH, which consists primarily of hGH-B. The physiological significance of this chemical heterogeneity is not clear, both in terms of the origin and the function of isohormones. Some possibilities for their physiological role are as follows: 1) individual isohormones may exhibit selective functions in the spectrum of hGH actions. 2) Isohormone-B may represent a pituitary storage form or prohormone which is enzymatically activated before or during secretion. 3) One or the other isohormone may be secreted, depending on the body's need. It is proposed to investigate these possibilities by: 1) studying the interaction of homogeneous hGH isohormones with established GH-responsive tissue (liver, adipose tissue and skeletal muscle), in terms of receptor binding and biological response, and in isolated pancreatic islets; 2) studying biosynthesis and secretion of hGH isohormones in pituitary organ culture, with direct comparison of secreted with stored products; 3) studying the isohormone nature of circulating and urinary hGH; 4) assessing the contribution of peripheral tissues to isohormone generation by in vitro and in vivo studies. It is also proposed to produce isohormone-specific antibodies and uniformly labeled hGH. The proposed studies should provide information on the bioactivity spectrum of individual isohormones, the biosynthetic events leading to the pituitary generation of isohormones, the exact nature of hGH in blood, the possible generation of isohormones in peripheral tissues, and the metabolic breakdown products of hGH, some of which may have biological activities of their own.